MSc (Applied Mathematics)) / Department of Mathematics and Applied Mathematics

INTRODUCTION: With the emergence of the COVID 19 pandemic, a new disease, Multisystem Inflammatory Syndrome in Children (MIS-C), had evolved. Increasing number of children are being reported to have MIS-C in the U.S. & worldwide. In the U.S. there are currently 2617 MISC cases reported. MIS-C & Kawasaki Disease (KD), have almost the same presentation, making clinical differentiation difficult. This study aims at differentiating KD & MIS-C which could assist clinicians to determine which one they could be dealing with in their practices. METHODS: Clinical features & laboratory values were collected from published studies found by queries on PubMed & other websites. Reported values were selected from published systemic reviews, meta-analyses, & large retrospective chart studies. RESULTS: In KD, the most prevalent clinical features are fever (100%) & the 5 KD-defining clinical features: oral mucosal changes (96.5%), rash (96%), non-purulent conjunctivitis (89%), extremity changes (75.6%), and cervical lymphadenopathy (62.7%). MIS-C also presents with fever (100%) but has lower prevalence of oral mucosal changes (23%), rash (38.2%), non-purulent conjunctivitis (44.0%), extremity changes (2.5%), & cervical lymphadenopathy (4%). MIS-C leads to higher rates of ventricular dysfunction (39.3%), myocarditis (23%), & shock. For cardiac biomarkers, MIS-C has elevated troponin I (x6 normal) & Beta Natriuretic Peptide (BNP) (x414 normal), while KD has elevations of troponin I (x1.9 normal) & BNP (x15 normal). MIS-C has higher elevations in ESR, CRP, and D-Dimer at x6, x30, and x40 from the normal values, respectively, while KD has elevations of x2.8, x2.1, x7.3 from the normal values, respectively. MIS-C is associated with neutrophilia, thrombocytopenia, & anemia in 22% of cases. KD is associated with mild neutrophilia & anemia. KD has thrombocytosis in the subacute phase (x1.46 normal). CONCLUSION: Our results demonstrated that there are overlaps & differences in clinical and laboratory features. Fever is present in both KD & MIS-C, however the 5 KD defining clinical features of KD are less frequent in MIS-C. MIS-C induces higher levels of troponin I & BNP, findings that could potentially explain for higher rates of ventricular dysfunction & myocarditis. MIS-C causes higher elevations in inflammatory markers & D-Dimers compared to KD. Uniquely, thrombocytopenia is commonly present in MISC rather than in KD. Differentiating KD & MIS-C can be challenging, but by focusing closely on the clinical & laboratory features, clinicians may be able to distinguish between the two &, therefore, deliver the most appropriate care to patients in their practices.

Although blood products are a great deal safer these days than in the past, patients receiving allogeneic blood transfusions are still exposed to potential hazards such as infectious diseases and immunomodulatory reactions. Therefore it is important to consider alternatives to allogeneic blood use. This can be done by means of blood conservation alternatives. A successful blood conservation program consists of three integrated phases, namely pre-operative, intra-operative and post-operative stages of patient care. The main objective of this study was to create a transfusion medicine database in order to evaluate the effect of a blood conservation program on the length of hospital stay of patients and the costs incurred in such a program. Five pilot hospitals who had implemented a blood conservation program were compared to five non-pilot hospitals (no blood conservation program). The results show that the average cost related to allogeneic blood usage in pilot hospitals amounted to R 473 274.13, compared to R 777 646.22 for the non-pilot hospitals. Length of hospital stay was also significantly lower in patients receiving blood conservation alternatives compared to patients receiving allogeneic blood. The total costs related to patients of blood conservation was lower, although not significantly, than the total costs of patients using allogeneic blood or both. In this study it was seen that the outcomes were positively associated with the implementation of blood conservation techniques. The efficacy of two leukodepletion methods for allogeneic blood products namely pre-storage and post-storage filtration, were evaluated. The results revealed that the mean leukocyte count of pre-storage leukodepleted blood samples (n = 30) was 0.12 cells/μl. The mean leukocyte count of the post-storage filtered blood samples (n = 20) was 0.05 cells/μl. Both methods were shown to be successful in the efficient removal of leukocytes. Copyright / Dissertation (MSc)--University of Pretoria, 2011. / Immunology / unrestricted

Abstract COVID-19, as named by the World Health Organization, is a disease caused by severe acute respiratory syndrome, coronavirus 2 (SARS CoV-2). This study is a spatiotemporal analysis of the COVID-19 pandemic in school-age children (5-18 years) in Washington and Johnson County, Tennessee and the possible relationship between public policies and the rate of infection. The first cases in Tennessee were documented in March 2020, with data being collected since that time. Daily data are accessible on the Tennessee Health Department COVID-19 dashboard with the number of new cases, hospitalizations, and deaths grouped by county in ages 5-11 years and 12-18 years. As this disease spread, government officials mandated different policies: mask mandates, stay at home, restrictions of public gatherings, and school closure, but many schools eventually allowed physical attendance. Emerging spatiotemporal hotspots are analyzed to identify the spatial clustering patterns of hot and cold spots with statistical significance using the Moran I statistical model in ArcGIS. The Change point detection tool in ArcGIS makes inferences about significant changes in trends over time; it was used to identify when significant changes occur. This is an ongoing project that will inform the approach I will adopt for my thesis, statistical tools will be used to determine the correlation between the time the change occurred and the implementation of policies, with an estimated 14-day lag time. Finally, the findings from both age groups will be compared. This study aims to help policymakers make better-informed decisions when responding to future pandemics.

Bakgrund: Smittsamma sjukdomar har funnits i alla tider. När sjuksköterskor möter patienter med smittsamma sjukdomar ska de tillhandahålla trygg vård som grundar sig på teoretisk och praktisk kunskap. I dag möter sjuksköterskor patienter som bär på Covid-19 som är en smittsam sjukdom. Forskning om vilka omvårdnadskompetenser som krävs för de som är i frontlinjen under en global katastrof är begränsade Syfte: Att beskriva sjuksköterskors erfarenheter av att vårda patienter med Covid-19. Metod: En litteraturöversikt baserad på 12 artiklar med både kvalitativ och kvantitativ ansats: Resultat: Ur analysen identifierades fyra teman; Vårda i ovisshet; Rädsla för smitta; Utmaningar att arbeta i skyddsutrustning och Stödets betydelse. Konklusion: Sjuksköterskor saknar information och erfarenhet av att arbeta med Covid-19. Trots att flertalet sjuksköterskor innehar specialistutbildningar räcker inte det för att bemästra denna pandemi. Sjuksköterskor som arbetar med Covid-19 löper en stor risk för yrkesmässig exponering som leder till en stark rädsla för smitta och att smitta sina familjemedlemmar. Utmaningar att arbeta i skyddsutrustning samt bristen på skyddsutrustning har lett till både psykiska och fysiska påfrestningar. Det har bevisats att familjen, teamet och arbetsgivaren är ett viktigt stöd för sjuksköterskor i denna pandemi. / Background: Infectious diseases have always existed. When nurses meet patients with infectious diseases, they should offer to provide care based on theoretical and practical knowledge. Today nurses meet the majority of patients carrying Covid-19 which is a contagious disease. Research on the nursing skills required for those at the forefront during a global disaster is limited: Aim: To describe nurses' experience of caring for patients with Covid-19: Method: A literature review based on 12 articles with both qualitative and quantitative approach: Results: From the analysis, four themes were identified; To nurture in uncertainty, Fear of infection, Challenges of working in protective equipment and The need of support: Conclusion: Nurses lack information and experience of working with Covid-19. Despite the fact that most nurses have specialist training, this is not enough to overcome this pandemic. Nurses who work with Covid-19 are at high risk for occupational exposure, which leads to a strong fear of infection and of infecting their family members. Challenges to work in protective equipment and the lack of protective equipment have lead to both mental and physical strain. It has been proven that the family, the team and the employer are an important support for nurses in this pandemic.

Parallel detection of antibodies with different specificity has many potential applications in epidemiological research, vaccine development and in the diagnosis of allergies, autoimmune and infectious diseases. Although ELISA-based tests are suitable for this purpose, available assays can be time consuming and require large quantities of both sample and reagents thus limiting their application for mass screening. / Revisión por pares

The U.S. aquaculture industry has become well established in the last three decades, and channel catfish aquaculture is the most significant component of this industry. Virulent Aeromonas hydrophila has been a serious disease problem since 2009 in the U.S. catfish aquaculture, and Aeromonas veronii and Edwardsiella piscicida are emerging pathogens of catfish. Therefore, this study aims to address fundamental questions on virulence mechanisms of these three fish pathogens, which I expect to support the development of control measures for preventing these diseases. In this study, E. piscicida and virulent Aeromonas hydrophila (vAh) genomes were sequenced, and comparative analyses were conducted using the genome sequences. Average nucleotide identity (ANI) calculations showed that E. piscicida strains share high sequence identity, yet they are from diverse host species and geographic regions. vAh isolates share very high sequence identity, while the other A. hydrophila genomes are more distantly related to this clonal group. We applied several comparative genomics approaches to evaluate E. piscicida genomes and E. ictaluri genomes, providing valuable information about unique and shared features of these two important pathogens in the Edwardsiella genus. Comprehensive secretion system analysis of 55 A. hydrophila genomes and deletion of tssD and tssI core elements of T6SS from vAh isolate ML09-119 has provided new knowledge. We sequenced the genome of virulent Aeromonas veronii strain ML09-123 from catfish indicated that it was highly similar to an A. veronii strain from China. Evaluation of all 41 A. veronii genomes available in the National Center for Biotechnology Information (NCBI) provides a base platform to investigate in detail the molecular mechanism of A. veronii biology and virulence. Lastly, we constructed deletion mutants vAhΔsia, vAhΔent, vAhΔcol, vAhΔhfq1, vAhΔhfq2, and vAhΔhfq1Δhfq2 to determine roles of A. hydrophila secreted proteins and regulatory proteins on virulence in catfish. Results showed that sialidase (vAhΔsia) and enterotoxin (vAhΔent) mutants were significantly attenuated.

Channel catfish farming is the largest aquaculture industry in the U.S., and virulent Aeromonas hydrophila is an important re-emerging bacterial pathogen of farmed catfish. A. hydrophila is ubiquitous in the aquatic environment and causes motile Aeromonas septicemia (MAS) in farmed catfish. A. hydrophila infection is challenging to treat due to rapidly progressive mass mortalities. Although florfenicol has been used in managing outbreaks, acute onset of anorexia, drug cost, and emergence of antimicrobial-resistant strains are significant concerns. Prevention of MAS by vaccination could be a promising approach, but a commercial vaccine is not available. Thus, it is critical to develop effective vaccines against A. hydrophila to prevent losses in the catfish industry. The overall objective of this study is to develop effective live attenuated A. hydrophila vaccines and understand macrophage-A. hydrophila interactions. To achieve this, potential virulence-related genes from T6SS, secretion pathway, tat pathway, and flagellar system were deleted by in-frame, and mutants’ virulence and protection were evaluated in channel catfish. Also, macrophage-A. hydrophila interactions were explored by studying global gene expression to understand macrophage responses to A. hydrophila and A. hydrophila virulence mechanisms

Myeloid-derived suppressor cells (MDSC) expand during sepsis, suppress both innate and adaptive immunity, and promote chronic immunosuppression, which characterizes the late/chronic phase of sepsis. We previously reported that the transcription factors Stat3 and C/EBPb synergize to induces the expression of microRNA (miR)-21 and miR-181b to promote MDSC expansion in a mouse model of polymicrobial sepsis that progresses from an early/acute proinflammatory phase to a late/chronic immunosuppressive stage. We also showed that Gr1+CD11b+ cells, the precursors of MDSCs, from mice genetically deficient in the inflammatory protein S100A9 lack miR-21 or miR-181b in late sepsis, and are not immunosuppressive. In the present study, we show that S100A9 induces miR-21 and miR-181b during the late sepsis phase. We find that S100A9 associates with and stabilizes the Stat3-C/EBPb protein complex that activates the miRNA promoters. Reconstituting Gr1+CD11b+ cells from the S100A9 knockout mice with late sepsis with S100A9 protein restores the Stat3-C/EBPb protein complex and miRNA expressions, and switches the Gr1+CD11b+ cells into the immunosuppressive, MDSC phenotype. Importantly, we find that this process requires IL-10 mediated signaling, which induces S100A9 translocation from the cytosol to the nucleus. These results demonstrate that S100A9 promotes MDSC expansion and immunosuppression in late/chronic sepsis by inducing the expression of miR-21 and miR-181b.

This study demonstrates the first case report in which an NK Cell deficiency initially presented as an asymptomatic disseminated herpes simplex viremia (HSV). A pre-term 13- day- old patient presented with disseminated HSV after investigation because his twin brother was found to have HSV vesicular lesions. The patient remained asymptomatic throughout the entire hospital course. While 40% of neonates never exhibit vesicular lesions, most of the infants will be symptomatic with DIC and/or respiratory and/or hepatic failure. The HSV development in his twin brother prompted immediate multiple HSV PCR testing even though he was asymptomatic. The results were positive for HSV in both plasma & nasopharynx. He received intravenous acyclovir treatment for 21 days. Both CSF & brain MRI studies demonstrated no CNS involvement. He was discharged home with oral acyclovir for one year. Two months after being off acyclovir he developed herpetic vesicles which resolved with acyclovir treatment. Currently, he is on chronic acyclovir treatment. Lymphocyte enumeration tests demonstrated NK cell deficiency. Typically, HSV is a virulent symptomatic infection especially when it presents with viremia. Here we have a case of asymptomatic HSV viremia. Likewise, HSV infection does not usually recur after 1 year of acyclovir treatment. Here, we have a child presenting with what seems to be recurrent congenital HSV infection even with adequate treatment. These atypical HSV presentations may have been due to NK cell deficiency. We, therefore, propose that clinicians should consider NK cell deficiency as possible etiology when HSV presents in an atypical manner as described in our case.